Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients.

Chronic electrical subthalamic nucleus (STN) stimulation is under investigation for alleviating parkinsonian symptoms. STN alterations may carry the risk of provoking abnormal involuntary movements (AIMs). We took advantage of the reversibility of the stimulation technique to assess the possibility of inducing AIMs, using different electrical variables with or without concomitant levodopa intake. Above a given threshold voltage, stimulation could induce contralateral distal mobile AIMs or hemiballism in the off-drug condition in two patients. AIMs occurred after a latency that varied from a few minutes up to several hours after switching on the stimulator. Hemiballism immediately disappeared upon switching off the stimulator. In these patients, levodopa had never provoked that type of AIMs before surgery. Levodopa-induced AIMs were not modified by electrical stimulation, but off-phase dystonia disappeared in one patient. Stimulation of the STN induced AIMs that resembled both those observed following spontaneous lesions of the STN and levodopa-induced diphasic AIMs in parkinsonian patients. As electrical stimulation provoked AIMs and antiparkinsonian benefit occurred with different electrical variables and different timing, the mechanisms responsible for these two effects could be distinct.

Bilateral subthalamic nucleus stimulation for severe Parkinson's disease.

Subthalamic nucleus (STN) lesions or high-frequency stimulations could improve parkinsonian symptoms in monkeys treated by MPTP. We have applied the procedure of chronic stimulation to the STN in severely disabled parkinsonian patients. This article presents the case of the first patient operated on bilaterally. Bilateral STN stimulation has greatly improved akinesia and rigidity. The benefit was maintained < or = 15 months after surgery. Unilateral stimulation induced motor effects mainly in contralateral limbs. Further studies are needed to evaluate the value of this procedure in the treatment of Parkinson's disease.

Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson's disease.

Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. To test this hypothesis, we studied the motor effect induced by three acute administrations of a dose of levodopa-benserazide (Madopar) with either 200 mg or 400 mg of tolcapone or placebo, in a double-blind latin-square design. The duration of the on-phase could be compared in 10 parkinsonian patients suffering from square-shaped motor effect. In comparison to placebo, 200 mg and 400 mg of tolcapone significantly increased the mean duration of the on-phase by 61.7 min ( +/- 19.4 SEM) and by 72.2 min ( +/- 18.5), respectively. This clinical effect is suggested to be related mainly to the increase in levodopa area under the curve and half-life induced by tolcapone. The intensity in dyskinesias was increased by 400 mg of tolcapone. Tolcapone appears to be well tolerated and could be helpful as an adjuvant treatment to levodopa in parkinsonian patients with motor fluctuations.

Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.

In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.

Deficits of cognitive executive functions in patients with sleep apnea syndrome.

Impairment of cognitive executive functions previously has been suspected to occur in association with sleep apnea syndrome (SAS), as suggested by some neuropsychological studies. However, such functions have not been assessed directly. In the present study, 17 patients with SAS were evaluated with various focused frontal lobe-related tests in comparison with 17 normal controls. Such tasks explored attention, short-term memory spans, learning abilities, planning and programming capacities, categorizing activities and verbal fluency. Patients were found to have a significantly decreased ability to initiate new mental processes and to inhibit automatic ones, in conjunction with a tendency for preservative errors. They were also affected with deficits of verbal and visual learning abilities and had reduced memory spans. Such defects were further evaluated via logistic regression against two criteria of the severity of the disease: the number of apneas and hypopneas per hour of sleep and the level of nocturnal hypoxemia. Memory deficits were rather related to the former, whereas typical frontal lobe-related abnormalities seemed rather consistent with the latter. These findings are discussed in light of data from the literature concerning cognitive impairments described for patients with isolated daytime sleepiness versus hypoxemia, as illustrated in other pathological or physiological circumstances.

Long-term prognosis of symptomatic lacunar infarcts. A hospital-based study.

BACKGROUND AND PURPOSE: This study concerns the long-term prognosis of lacunar infarcts. METHODS: We report the analysis of our hospital-based series of 178 patients consecutively admitted for a lacunar syndrome due to a lacunar infarct diagnosed with computed tomography and magnetic resonance imaging. Demographic data, medical history, vascular risk factors, and imaging data were recorded for each patient. The follow-up was 35 +/- 22 months. RESULTS: The lacunar syndrome was pure motor hemiparesis in 69 patients (39%), ataxic hemiparesis in 45 patients (25.4%), pure sensory stroke in 15 patients (8.5%), sensorimotor stroke in 14 patients (7.9%), and miscellaneous syndrome in 34 patients (19.2%). The 4-year survival rate was 80 +/- 4% and the 4-year survival rate without recurrent stroke was 85 +/- 3.5%. Using Cox proportional-hazards analysis, the predictors of death were age (P < .02), diabetes mellitus (P < .05), and cigarette smoking (P < .05). We did not find any predictors of recurrence. After 1 year, 74% of the patients had mild or no disability. Using logistic regression analysis, the predictive factors of disability were age more than 70 years (P < .01), diabetes (P < .01), history of stroke or transient ischemic attack (P < .05), and type of lacunar syndrome (P < .01). Imaging data, number of lacunes, and presence of leukoaraiosis were not predictors of outcome. CONCLUSIONS: Our study suggests that with a high survival rate, a low recurrence rate, and a relatively good functional recovery, lacunar infarcts have a relatively favorable prognosis.

Reproducibility of motor effects induced by successive subcutaneous apomorphine injections in Parkinson's disease.

We performed a crossover study of apomorphine-induced motor response reproducibility in 10 parkinsonian patients with the "on-off" phenomenon. On 2 separate days, each patient received two successive identical s.c. apomorphine injections, the second injection being randomly administered either 10 or 80 min after the end of the first apomorphine-induced motor benefit. Latency (12.3 +/- 4.5 min) and duration (61.9 +/- 13.3 min) of motor effects were similar in all tests. A transient worsening of the parkinsonian state after a motor improvement induced by apomorphine occurred in most of the patients. Therefore, the duration and severity of the "off" period after a motor improvement does not seem to influence the efficacy of a second apomorphine administration.

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.